chr20-10252404-C-G

Variant names:

• chr20-10252404-C-G
• rs12626080
• NM_130811.4:c.-63-23025C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130811.4(SNAP25):​c.-63-23025C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,010 control chromosomes in the GnomAD database, including 21,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21919 hom., cov: 33)
• Consequence: SNAP25 NM_130811.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 7 publications found

Genes affected

SNAP25 (HGNC:11132): (synaptosome associated protein 25) Synaptic vesicle membrane docking and fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, one of which is supplied by v-SNARE and the other three by t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and the protein encoded by this gene contributes the other two. Therefore, this gene product is a presynaptic plasma membrane protein involved in the regulation of neurotransmitter release. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP25	NM_130811.4	c.-63-23025C>G		intron_variant	Intron 1 of 7	ENST00000254976.7	NP_570824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP25	ENST00000254976.7	c.-63-23025C>G		intron_variant	Intron 1 of 7	1	NM_130811.4	ENSP00000254976.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80819 AN: 151892 Hom.: 21908 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80877 AN: 152010 Hom.: 21919 Cov.: 33 AF XY: 0.522 AC XY: 38808 AN XY: 74276

African (AFR) AF: 0.521 AC: 21627 AN: 41486

American (AMR) AF: 0.502 AC: 7673 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2045 AN: 3466

East Asian (EAS) AF: 0.255 AC: 1322 AN: 5176

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4820

European-Finnish (FIN) AF: 0.458 AC: 4822 AN: 10530

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39383 AN: 67944

Other (OTH) AF: 0.538 AC: 1137 AN: 2112

Alfa AF: 0.539 Hom.: 2823

Bravo AF: 0.533

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12626080; hg19: chr20-10233052;